1. Field of the Invention
This invention relates generally to a novel sustained-release formulation which gradually releases a medicinal agent therefrom. More specifically, the invention pertains to the use of the formulation for slowly dispensing a drug in the eye.
2. Description of Related Art
It is basically known in the art that medicinally active substances may be dissolved in the aqueous constituent of hydrogels to gradually release such substances over an extended period. For example, U.S. Pat. No. 3,220,960 describes utilizing a hydrogel in the eye as a carrier for time release medicaments such as boric acid or penicillin. Similarly, U.S. Pat. Nos. 3,551,556; 3,641,237; 4,003,991; and 4,271,143 disclose slowly releasing an active ingredient from an insoluble, cross-linked hydrogel in one form or another. Several compositions illustrated in the latter two patents are comprised of viscous, long-acting gel preparations where the prolongation of biological activity of the ophthalmic drug results from a slow erosion of the gel surface. The formulation in U.S. Pat. No. 3,551,556 shows granular non-ionogenic, neutral, insoluble hydrogels which are useful for oral or intramuscular application. Further, many patents are directed to ocular insert devices which prolong the effect of a drug incorporated within the device. Such patents include U.S. Pat. Nos. 3,811,444; 3,826,258; and 3,786,812.
These prior carriers of medicaments present certain difficulties during their use, particularly with ophthalmic drugs. The predominant complaint with long-acting gel formulations is blurred vision. Another difficulty is the inability to wear corrective contact lenses when a viscous material will be instilled and remain in the eye over an extended period of time. The ocular insert devices also present certain disadvantages with their use. When inserted into the conjunctival sac, such devices create a strong foreign body sensation and discomfort for the patient. The insert devices must be changed weekly. Additionally, the devices tend to fall out of the eye easily and cannot be used further by the patient since they are not capable of being sterilized.
Similarly, conventional contact lenses containing a sustained-release medicine carrier have drawbacks in practice. They have been found to obtain inadequately controlled or prolonged release characteristics making the conventional lenses unsuitable and impractical as sustained-release devices. The concept of soaking a high water content material in a drug solution has been used with conventional hydroxyethyl methacrylate based contact lenses, for example, a polymerized hydrophilic monomer or soft contact lens such as Soflens.RTM. manufactured by Bausch & Lomb. See Ruben et al., British J. Ophthal., 59:455 (1975). In practice, Soflens.RTM., however, provides an inefficient system and is an unsuitable device for prolonged release. Experimental studies have shown that Soflens.RTM. will release 100% of pilocarpine hydrochloride in buffered saline and distilled water in merely 11/2 and 21/2 hours, respectively.